Systemic arterial pressure regulation is vital for normal functioning of the brain and other internal organs in mammals. In a simplified form, the pressure is determined by the balance of forces between pumping force generated by the heart's muscle and mechanical resistance of arterial blood vessels. Thus, the pressure decreases when either the pumping force of the heart or arterial resistance decreases; it rises when the pumping activity of the heart or vascular resistance increase.
This large-scale, simplified concept of arterial pressure regulation has proved useful for pinpointing the primary factors responsible for abnormal pressure variations and designing therapies that target those factors to restore normal pressure. In particular, when arterial pressure exceeds normal limits and becomes too low or too high, a number of specific, “cardioactive” medications can be administered to increase or decrease pumping activity of the heart. On one side of the spectrum of cardioactive medications are beta-blockers and calcium blockers that diminish heart's activity and, therefore, decrease arterial pressure. On the other side are dobutamine and norepinephrine that produce an opposite effect. Another class of medications, referred to as the vasoactive medications, modifies the activity of smooth muscles in the vascular walls (vasomotor activity/tone, VMA), thus changing the size of the vascular lumen. Those medications include vascular smooth-muscle relaxants that increase vascular lumen, causing arterial pressure to decline, as well vascular smooth-muscle stimulants that decrease vascular lumen, increasing both vascular resistance and arterial pressure.
The relationship between arterial pressure and vascular properties described above can be also useful for clinical, physiological and pharmacological testing of new medications as well as designing new treatments for subjects with various cardiovascular disorders. Herein, the term subject denotes a living being, including human beings and animals. In particular, medications causing vascular relaxation have proved useful for treatment of patients with heart failure (HF) and dyspnea, who demonstrate a number of improvements in response to vasoactive medications, such as serelaxin (Teerlink et al.; RELAXin in Acute Heart Failure (RELAX-AHF) Investigators. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2013; 381: 29-39.).
However, the overall effect of vasoactive medications in the studied patient populations has been modest or not statistically significant, suggesting that the magnitude of the responses to vasoactive substances varies from patient to patient and could be completely absent in some individuals. Indeed, Teerlink et. al. have shown that improvements in dyspnea are more likely to occur in the HF patients who have higher baseline arterial pressure (Teerlink et al. Vasodilators in Acute Heart Failure (AHF): Does Blood Pressure Matter? Results from Pre-Relax-AHF. Journal of Cardiac Failure 2009; 15:S74). This observation could have been expected, because higher arterial pressure is usually associated with higher peripheral (vascular) resistance, which is caused by greater VMA, as described above. Greater VMA, in turn, would result in more pronounced vasodilation in response to serelaxin or other vasorelaxants (or functional tests associated with vascular relaxation, e.g., exercise stress test) compared with subjects who have a low VMA. Thus, by examining baseline VMA, one can predict the magnitude of vasoactive response, identify subjects who would benefit the most from vasoactive medications and optimize (fine tune) dose/frequency of the drug intake for each subject.